G protein-coupled receptor 39 (GPR39) (GPR39)

G protein-coupled receptor 39 (GPR39), also known as the zinc-sensing receptor (ZnR), is a Class A GPCR that mediates cellular responses to extracellular zinc ions (Hershfinkel et al., 2001). Upon activation, GPR39 triggers the Gq-protein-mediated phospholipase C (PLC) pathway, resulting in the production of inositol trisphosphate (IP3) and the subsequent release of intracellular calcium (Ca2+) (Popovics & Stewart, 2011). This signaling cascade further activates the mitogen-activated protein kinase (MAPK/ERK) and phosphoinositide 3-kinase (PI3K/AKT) pathways, which are essential for regulating cell survival, proliferation, and differentiation (Sunuwar et al., 2017). GPR39 is expressed in diverse tissues, including the brain, pancreas, and gastrointestinal tract, where it plays roles in neuroprotection, insulin secretion, and epithelial barrier integrity (Mazzocchi et al., 2015). Due to its involvement in depression, type 2 diabetes, and inflammatory bowel disease, GPR39 has emerged as a significant therapeutic target (Mlyniec, 2015). Small molecule agonists like TC-G 1008 have been developed to explore its potential in treating metabolic and neuropsychiatric disorders (Peukert et al., 2014). However, its pro-proliferative role in certain cancers necessitates careful evaluation of its safety as a drug target (Liu et al., 2015).

Other names

Zinc-sensing receptorZnRG-protein coupled receptor 39

Agonism of GPR39 activates the Gq/PLC/IP3/Ca2+ signaling axis and downstream ERK/AKT pathways to modulate cellular physiological responses.